Endothelial TGF-β signalling drives vascular inflammation and atherosclerosis

Pei Yu Chen, Lingfeng Qin, Guangxin Li, Zheng Wang, James E. Dahlman, Jose Malagon-Lopez, Sharvari Gujja, Nicholas A. Cilfone, Kevin J. Kauffman, Lele Sun, Hongye Sun, Xinbo Zhang, Binod Aryal, Alberto Canfran-Duque, Rebecca Liu, Pascal Kusters, Alfica Sehgal, Yang Jiao, Daniel G. Anderson, Jeffrey GulcherCarlos Fernandez-Hernando, Esther Lutgens, Martin A. Schwartz, Jordan S. Pober, Thomas W. Chittenden, George Tellides, Michael Simons

Research output: Contribution to journalArticlepeer-review

Abstract

Atherosclerosis is a progressive vascular disease triggered by interplay between abnormal shear stress and endothelial lipid retention. A combination of these and, potentially, other factors leads to a chronic inflammatory response in the vessel wall, which is thought to be responsible for disease progression characterized by a buildup of atherosclerotic plaques. Yet molecular events responsible for maintenance of plaque inflammation and plaque growth have not been fully defined. Here we show that endothelial transforming growh factor β (TGF-β) signalling is one of the primary drivers of atherosclerosis-associated vascular inflammation. Inhibition of endothelial TGF-β signalling in hyperlipidemic mice reduces vessel wall inflammation and vascular permeability and leads to arrest of disease progression and regression of established lesions. These proinflammatory effects of endothelial TGF-β signalling are in stark contrast with its effects in other cell types and identify it as an important driver of atherosclerotic plaque growth and show the potential of cell-type-specific therapeutic intervention aimed at control of this disease.

Original languageEnglish (US)
Pages (from-to)912-926
Number of pages15
JournalNature Metabolism
Volume1
Issue number9
DOIs
StatePublished - Sep 1 2019

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Cell Biology
  • Physiology (medical)

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